This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Important progress has been made in the past reporting period. RTI-336, a compound first tested and characterized in our laboratory and has been approved for Phase I clinical trials in humans. It is expected to be a medication for psychostimulant (cocaine, amphetamine, and methamphetamine) abusers and addicts. As of this writing, no toxic effects were found that preclude further study, and additional studies are planned in humans. The utilization of PET (positron emission tomography) scanning is often important for addressing problems in medications development. In practice, the PET procedure has been limited to measuring levels of proteins or percentage occupancy. From studies of protein turnover and half-lives published earlier, it has been suggested that PET procedures be expanded to include turnover measurements of relevant proteins in animals. This will provide a more comprehensive view of the involvement of various proteins than is possible by measuring levels alone.